Analisis Mutasi Gen Pengkode Reverse Transcriptase (RT) HIV-1 pada Pasien yang Diterapi RT Inhibitor di Papua dan Papua Barat

Angela Puspa Larasati, Dr. rer. nat. Abdul Rahman Siregar, S.Si., M.Biotech.; Hotma Martogi Lorensi Hutapea, M.Si

2025 | Skripsi | BIOLOGI

Persebaran Human Immunodeficiency Virus type 1 (HIV-1) di Papua semakin tinggi dengan salah satu penyebabnya adalah kegagalan Terapi Antiretroviral (ARV). Mutasi pada gen pengkode reverse transcriptase terbukti bisa mengubah struktur RT sehingga menyebabkan resistensi terhadap obat Nucleoside Reverse Transcriptase Inhibitors (NRTI) dan Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI). Penelitian ini bertujuan untuk mengetahui mutasi gen pengkode reverse transcriptase (RT), pengaruh mutasi terhadap efektivitas inhibitor RT, dan frekuensi resistensi HIV terhadap inhibitor RT pada ODHA di Papua dan Papua Barat. Analisis mutasi, resistensi, dan subtipe dilakukan dengan mengacu kepada Standford HIVdb. Hasil analisis subtipe dikonfirmasi dengan COMET HIV, NCBI, dan Geno2pheno. YASARA dan FoldX digunakan untuk pembuatan sekuens RTase mutan. Molecular docking dilakukan menggunakan AutoDock Tools dan PyRx, sedangkan visualisasinya menggunakan PyMOL dan  Discovery Studio Visualizer. Pada penelitian ini, frekuensi resistensi HIV pada subyek adalah 28.57% subyek mengalami resistensi hanya obat NRTI, 57.14% subyek mengalami resistensi obat NRTI dan NNRTI. Frekuensi kemunculan mutasi NRTI tertinggi adalah S68G, M184V, K65R, V75M dan L74I. Frekuensi kemunculan mutasi NNRTI tertinggi adalah K103N, G190A, P225H, K238T, dam Y188L. Kemunculan mutasi NRTI dan NNRTI menyebabkan perubahan afinitas ikatan dan interaksi molekuler antara RTI dengan RTase sehingga mempengaruhi tingkat efektivitas obat RTI terhadap subyek. 

The prevalence of Human Immunodeficiency Virus type 1 (HIV-1) in Papua is increasing, with one of the contributing factors is treatment failure of Antiretroviral Therapy (ARV). Mutations in the reverse transcriptase (RT) gene have been shown to alter the structure of RT, thereby causing resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI). This study aims to identify mutations in the reverse transcriptase (RT) coding gene, the impact of mutations on the effectiveness of RT inhibitors, and the frequency of HIV resistance to RT inhibitors among people living with HIV (PLWHA) in Papua and West Papua. Analysis of mutations, resistance, and subtypes was conducted using the Stanford HIVdb. Subtype analysis results were validated using COMET HIV, NCBI, and Geno2pheno. YASARA and FoldX were used for constructing RTase mutant sequences. Molecular docking was conducted with AutoDock Tools and PyRx, while visualizations were displayed with PyMOL and  Discovery Studio Visualizer. In this study, the frequency of HIV resistance among subjects was 28.57% for NRTI-only resistance and 57.14% for NRTI and NNRTI resistance. The most frequently identified NRTI mutations were S68G, M184V, K65R, V75M, and L74I. The most frequently identified NNRTI mutations were K103N, G190A, P225H, K238T, and Y188L. The appearance of NRTI and NNRTI mutations led to changes in the binding affinity and molecular interactions between RTI and RTase, thereby affecting the effectiveness of RTI drugs in subjects.

Kata Kunci : HIV; Molecular docking; Mutasi; Reverse transcriptase, Terapi Antiretroviral